This is a proposal to continue the Coronary Artery Risk Development in Young Adults (CARDIA) Study for the period 2003-8. CARDIA is a population-based observational study of African-American and white men and women of diverse socioeconomic status that began by examining 5115 young adults aged 18-30 in 1985-6. Follow-up examinations at years 2, 5, 7, 10, and 15 achieved high retention rates, collected a rich set of high quality data and stored specimens bearing on the causes of cardiovascular disease (CVD), and led to 166 peer-reviewed publications. During the next 5 years we will continue semi-annual telephone contacts, disease event surveillance, and analysis and publication activities. We will carry out a year 20 exam on our cohort, who will be 38-50 years old. We propose to re-examine at least 73% of those surviving (3650 participants study-wide and 989 in Minneapolis) with 4 main objectives: 1) To identify predictors of development and progression of subclinical atherosclerosis, we will measure risk factor levels (established, novel, lifestyle, and psychosocial) and subclinical atherosclerosis (coronary artery calcification [CAC] and carotid intima-media thickness [IMT]). We will examine the antecedents of the risk factors with special attention to the growing epidemic of obesity, explore the effects of recent and remote risk factor exposure on CAC, on CAC progression, and on IMT, and assess the role of conditions such as obesity, diabetes and renal impairment, and of differences in socioeconomic status and health care access and utilization. 2) To elucidate possible racial differences in CVD pathogenesis, we will compare the factors associated with CAC incidence and prevalence, and with IMT prevalence, across risk-gender groups. We will explore factors that may explain observed differences. 3) To test whether inflammation precedes subclinical disease, we will examine the time course of the association between inflammatory markers (such as C-reactive protein) and CAC and IMT evidence for atherosclerosis. We will also identify predictors of inflammation (such as infection), and the impact of obesity and of visceral adiposity. 4) To assess the roles of genetic variation and gene-by-environment interactions in CVD pathogenesis, we will explore their role in the etiology of risk factors, and test if allelic variation in genes such as those regulating obesity, hyperlipidemia, blood pressure, and bone mineralization are associated with CAC and IMT. These data, as well as findings in separately funded ancillary studies, will allow us to examine the antecedents and prevalence of subclinical atherosclerosis in diverse populations. We will analyze the role of predisposing genetic traits in the presence of behavioral and physiologic risk factors in order to detect genotype-by-environment interactions, and to study how these differ in men and women, and in African-Americans and whites. The proposed activities will take full advantage of CARDIA's outstanding database and specimen bank, and our team of investigators, organizational structure, and quality control procedures. We will expand the pool of investigators contributing to design, analysis and publication activities by involving new scientists in CARDIA, and we will enhance dissemination of CARDIA data and analytic support to non-affiliated investigators. These plans will accelerate the growth of our understanding of the 20-year antecedents of middle-aged risk factors and subclinical disease. This knowledge is needed for designing preventive medicine policies that address the growing epidemic of obesity and reduce the public health burden of CVD, and that are tailored to specific population subgroups and settings where they will be most effective.